Drug Delivery Device

ABSTRACT

A drug delivery device for setting and dispensing a dose of a drug is presented having a support body having a first end defining a first opening and a second end defining a second opening and a centered outer indicator ring. A syringe barrel sealed by a stopper is slidably diposed therein along an axial direction and adapted to have an integrated needle or to be coupled with a needle assembly, wherein the syringe barrel is positioned within the support body. A needle shield is adapted to be coupled to one fo the ends of the support body and slidably disposed thereon. An outer body is adapted to be coupled to the other end of the support body and slidably disposed thereon, wherein the outer indicator ring limits the movement of the outer body as well as of the needle shield.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 14/412,731, filed on Jan. 5, 2015, which is the national stageentry of International Patent Application No. PCT/EP2013/065128, filedon Jul. 17, 2013, which claims priority to U.S. Application No.61/714,984, filed on Oct. 17, 2012 and European Application No.E12176674.5, filed on Jul. 17, 2012. The entire disclosure contents ofthese applications are herewith incorporated by reference into thepresent application.

TECHNICAL FIELD

The present invention relates to drug delivery device with inherentneedle safety comprising a pre-filled syringe.

BACKGROUND

Pre-filled syringes that are filled with a selected dosage of amedicament are well known injection devices for administering themedicament to a patient. Drug delivery devices comprising a needleshield for covering a needle of a pre-filled syringe before and afteruse are also well known. Typically, the needle shield is either manuallymoved or moved by the action of a relaxing spring to surround theneedle.

A different type of drug delivery device known in the state of the artsolves the object of providing needle safety by arranging the pre-filledsyringe movable relative to a body, whereas the pre-filled syringe isretracted into the body after the injection.

SUMMARY

It is an object of the present invention to provide an improved drugdelivery device.

The object is achieved by a drug delivery device according to claim 1.

Preferred embodiments of the invention are given in the dependentclaims.

In the context of this specification, the terms distal and proximal aredefined from the point of view of a person performing an injection.Consequently, a distal direction refers to a direction pointing towardsthe body of a patient receiving an injection and a distal end defines anend of an element that is directed towards the body of the patient.Respectively, the proximal end of an element or the proximal directionis directed away from the body of the patient receiving the injectionand opposite to the distal end or distal direction.

According to the invention a drug delivery device for setting anddispensing a dose of a drug comprises:

-   -   a support body having a first end defining a first opening and a        second end defining a second opening and a centered outer        indicator ring,    -   a syringe barrel sealed by a stopper slidably disposed therein        along an axial direction and adapted to have an integrated        needle or to be coupled with a needle assembly, wherein the        syringe barrel is positioned within the support body,    -   a needle shield adapted to be coupled to one of the ends of the        support body and slidably disposed thereon;    -   an outer body adapted to be coupled to the other end of the        support body and slidably disposed thereon;    -   wherein the outer indicator ring limits the movement of the        outer body as well as of the needle shield.

The drug delivery device according to the invention is particularlyshort and has a low part count.

In an exemplary embodiment the outer indicator ring is designed as acircumferential rib. Alternatively, the outer indicator ring may bedesigned as at least one circumferential rib section.

In an exemplary embodiment the outer indicator ring may be curved.

A first detent mechanism may be arranged to constrain movement of theouter body relative to the support body by opposing this movement with afirst detent force. This avoids a so called wet injection with drugleaking out of the tip of the needle during needle insertion beforereaching the insertion depth.

A second detent mechanism may be arranged to constrain movement of theneedle shield relative to the support body by opposing this movementwith a second detent force. This prevents inadvertent exposure of theneedle by shaking or reversing the drug delivery device prior toapplication against the injection site.

The first detent force may be greater than a sum of the second detentforce and a counteracting force of a needle shield spring arranged tobias the needle shield against the support body. This allows for aphased movement of the drug delivery device. When applied against theinjection site the needle shield will move first for inserting theneedle into the injection site. On further depression the outer bodymoves for delivering the drug.

The second detent mechanism may comprise at least one guiding trackdefined on the support body and at least one retaining clip on theneedle shield deflectable by the guiding track, wherein the guidingtrack is configured such that the retaining clip follows a first pathwhen the needle shield is depressed for needle extension and a differentsecond path when the needle shield is subsequently extended, wherein anon-return catch is arranged for catching the retaining clip at the endof the second path. Thus, re-exposure of the used needle is prevented.

The second detent mechanism may likewise be independent from the guidetrack with the catch and the retaining clips.

The support body may comprise outer guiding means protruding radiallyoutwards for guiding the movement of the outer body or the support bodymay comprise a guiding slot disposed within the wall of the support bodyfor guiding the movement of the needle shield. The support body andouter body are thus keyed and prevented from rotating independently.

In an exemplary embodiment a plunger rod is coupled to the stopper,wherein a proximal portion of the plunger rod is adapted to be coupledto the outer body.

The needle shield may be arranged as one part or it may comprise atleast a body section and a cap part. The cap part of the needle shieldis rotationally locked to the body section. This may be achieved by thecap part having a non-circular, e.g. elliptical cross section engagingin a corresponding opening in the body section.

In an exemplary embodiment the outer body may be formed as a single partor the outer body may comprise at least a base section and a cap part.

The plunger rod may comprise a flange to engage a barrel collar of thesyringe barrel.

The end of the outer body coupled to the support body may comprise aradially outwards directed flange thus improving ergonomics whenapplying the drug delivery device.

In an exemplary embodiment a direction indicator designed as a profiledcavity or concavity in the surface of the outer body may be arranged inthe range of the flange.

The needle shield may likewise comprise a direction indicator.

The ends of the outer body and the needle shield coupled to the supportbody may have mating surfaces. Mating surfaces, particularly also matingwith the shape of the indicator ring visually and haptically indicate tothe user that the respective parts are intended to be pushed completelytogether so that the mating parts abut in order to correctly apply thedrug delivery device.

The support body may comprise a radially inwards-directed rib to retainthe barrel collar thus fixing the syringe barrel in axial translationwith respect to the support body.

The length of the support body may approximately correspond with thecombined length of the outer body and the needle shield.

The term “drug” or “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exendin-3 or exendin-4 or an analogue or derivative ofexendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 Exendin-4(1-39),

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDa) that are also knownas immunoglobulins which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and δ approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (C_(H)) and the variable region (V_(H)). Inone species, the constant region is essentially identical in allantibodies of the same isotype, but differs in antibodies of differentisotypes. Heavy chains γ, α and δ have a constant region composed ofthree tandem Ig domains, and a hinge region for added flexibility; heavychains μ and ε have a constant region composed of four immunoglobulindomains. The variable region of the heavy chain differs in antibodiesproduced by different B cells, but is the same for all antibodiesproduced by a single B cell or B cell clone. The variable region of eachheavy chain is approximately 110 amino acids long and is composed of asingle Ig domain.

In mammals, there are two types of immunoglobulin light chain denoted byA and K. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H—H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts.

Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g.salts having a cation selected from alkali or alkaline, e.g. Na+, or K+,or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4independently of each other mean: hydrogen, an optionally substitutedC1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, anoptionally substituted C6-C10-aryl group, or an optionally substitutedC6-C10-heteroaryl group. Further examples of pharmaceutically acceptablesalts are described in “Remington's Pharmaceutical Sciences” 17. ed.Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., U.S.A.,1985 and in Encyclopedia of Pharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE FIGURES

The present invention will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus, are not limitiveof the present invention, and wherein:

FIG. 1 is a perspective view of a drug delivery device comprising asupport body, an outer body and a needle shield,

FIG. 2 is a longitudinal section of the drug delivery device in a firstsection plane,

FIG. 3 is a longitudinal section of the drug delivery device in a secondsection plane,

FIG. 4 is an exploded perspective view of the outer body,

FIG. 5 is a longitudinal section of the support body,

FIG. 6 is an exploded perspective view of the needle shield,

FIG. 7 is a lateral view of the drug delivery device prior to aninjection,

FIG. 8 is a lateral view of the drug delivery device during needleinsertion,

FIG. 9 is a lateral view of the drug delivery device at the end ofinjection,

FIG. 10 is a lateral view of the drug delivery after needle retraction,and

FIG. 11 is a schematic view of the drug delivery device with a bootremover for removing the protective needle boot prior to an injection.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIG. 1 is a perspective view of a drug delivery device 1 comprising asupport body 2, an outer body 3 and a needle shield 4, all of themhaving an essentially tubular shape. FIG. 2 is a longitudinal section ofthe drug delivery device 1 in a first section plane. FIG. 3 is anotherlongitudinal section of the drug delivery device 1 in a second sectionplane approximately 90° offset from the section plane in FIG. 2. Aproximal end of the support body 2 is telescoped in the outer body 3 anda distal end of the support body 2 is telescoped in the needle shield 4.A syringe barrel 5 is slidably arranged within the support body 2, thesyringe barrel 5 defining an inner cavity for a dose of a drug. A hollowinjection needle 6 is arranged on a distal end of the syringe barrel 5.A stopper 7 is slidably arranged within the syringe barrel 5 for sealingits proximal end and for displacing the drug from the syringe barrel 5through the injection needle 6. A plunger rod 8 is arranged within theouter body 2 for engaging the stopper 7. The plunger rod 8 may bescrewed or snapped into the stopper 7. A needle shield spring 9 isarranged for biasing the needle shield 4 in the distal direction Dagainst the support body 2.

FIG. 4 is an exploded perspective view of the outer body 3. The outerbody 3 comprises a tubular base section 3.1 and a cap part 3.2 forclosing the proximal end of the base section 3.1. The cap part 3.2 isengageable to the base section 3.1 by a snap fit 3.3 (cf. FIG. 3). Thebase section 3.1 comprises two ribs 3.4 (cf. FIG. 2) extending inwardlyfrom an inner surface of the base section 3.1 on opposite sides forrespectively sliding along a guiding slot 2.1 in the support body (cf.FIG. 1). The cap part 3.2 has a central peg 3.5 for engaging the plungerrod 8 when the drug delivery device 1 is assembled. The central peg 3.5may either abut the plunger rod 8 or be attached to it. The outer body 3is movable in a distal direction D and in a proximal direction P withrespect to the support body 2.

The syringe barrel 5 is inserted into the support body 2. A proximalbarrel collar 5.1, sometimes referred to as a finger flange, on thesyringe barrel 5 serves for attaching the syringe barrel 5 to thesupport body 2 by distally abutting an internal rib 2.4 in the supportbody 2 so that the syringe barrel 5 is fixed towards the distaldirection D in its axial position with respect to the support body 2.The syringe barrel 5 is also fixed towards the proximal direction P bytwo resilient non-return clips 2.5 which are deflected by the barrelcollar 5.1 when assembling the syringe barrel 5 into the support body 2and snap in place once the barrel collar 5.1 has passed them thusfacilitating assembly.

FIG. 5 is a longitudinal section of the support body 2. The support body2 comprises a indicator ring 2.2 in the shape of radially outwardsprotruding and essentially circumferential rib. The indicator ring 2.2may cover part of or the whole circumference of the support body 2. Theindicator ring 2.2 is arranged to interact with the needle shield 4 soas to limit distal movement of the support body 2 with respect to theneedle shield 4. A guiding track 2.3 is arranged in an outer surface ofthe support body 2 at the distal end for interacting with the needleshield 4 for limiting axial movement of the support body 2 with respectto the needle shield 4. The guiding track 2.3 comprises a distalinclined section 2.3.1, a longitudinal section 2.3.2, a proximalinclined section 2.3.3 and a non-return catch 2.3.4. Near the proximalend of the support body 2 two resilient snap arms 2.6 for interactingwith the outer body 3 are arranged. The resilient snap arms 2.6initially engage the outer body 3 near its distal end in such a mannerthat the outer body 3 and the support body 2 are axially coupled unlessa first detent force is applied, which deforms the resilient snap arms2.6 so that the outer body 3 decouples from the support body 2 and canmove relative to the support body 2 in the distal direction D.

FIG. 6 is an exploded perspective view of the needle shield 4. Theneedle shield 4 comprises a tubular body section 4.1 and a cap part 4.2with a central opening 4.3. The cap part 4.2 is engaged to the bodysection 4.1 by a snap fit 4.4 (cf. FIG. 3) thus preventing relativeaxial movement. Two resilient retaining clips 4.5 with a respectiveinward protrusion 4.7 are arranged on the cap part 4.2. The inwardprotrusions 4.7 engage the guiding track 2.3 in the support body 2 so asto restrict relative axial movement between the needle shield 4 and thesupport body 2. A protective needle boot (not illustrated) may bepositioned in and/or through the central opening 4.3 of the cap part 4.2before and after an injection. The cap part 4.2 is rotationally lockedto the body section 4.1. This may be achieved by the cap part 4.2 havinga non-circular, e.g. elliptical cross section engaging in acorresponding opening in the body section 4.1.

FIG. 7 is a lateral view of the drug delivery device 1 prior to aninjection. The outer body 3 is fully extended in the proximal directionP from the support body 2. The needle shield 4 is fully extended fromthe support body 2 in the distal direction D. The injection needle 6 isin a retracted position within the needle shield 4. The needle shieldspring 9 is relaxed. In this situation the inward protrusion 4.7 islocated distally from the distal inclined section 2.3.1 of the guidingtrack 2.3 so that the resilient retaining clips 4.5 are also relaxed.

A user may grab the outer body 3 and push the proximal end of the needleshield 6 against an injection site, e.g. a patient's skin. The forcefrom the user's hand is resolved through the outer body 3, the resilientsnap arm 2.6, the support body 2, the inclined section 2.3.1 of theguiding track 2.3 and the retaining clips 4.5 into the needle shield 4.The retaining clips 4.5 engaging the inclined section 2.3.1 of theguiding track 2.3 provide a second detent force which has to be overcomein order to move the needle shield 4 against the support body 2. As theuser applies a sufficiently high force exceeding the second detent forcethe needle shield 4 is moved in the proximal direction P with respect tothe support body 2 and all other parts of the drug delivery device 1thereby also compressing the needle shield spring 9 so that the drugdelivery device 1 arrives in a state as illustrated in FIG. 8. At thesame time, the retaining clips 4.5 are deflected in a first tangentialdirection T1 by the inclined section 2.3.1 and the inward protrusions4.7 travel up the longitudinal section 2.3.2 in the proximal directionP. Once the inward protrusion 4.7 has travelled proximally beyond thelongitudinal section 2.3.2 the retaining clips 4.5 are no longerdeflected. Hence, they will relax into a position proximally from theproximal inclined section 2.3.3 so the inward protrusion 4.7 isprevented from travelling the same way back on subsequent extension ofthe needle shield 4. The first detent force is greater than the sum ofthe second detent force and the counteracting force of the needle shieldspring 9 at full depression of the needle shield 4 such that onapplication of the drug delivery device 1 against the patient's skin theneedle shield 4 always moves prior to the outer body 3 relative to thesupport body 2. This movement is opposed by the friction force of theinjection needle 6 when penetrating the skin. In order to avoid a socalled wet injection with drug leaking out of the tip of the needleduring needle insertion before reaching the insertion depth the frictionforce of the needle 6 must be less than the counteracting force of thestopper 7 due to friction between the stopper 7 and the inner wall ofthe syringe 5 and due to the hydrostatic resistance of the drug to bedisplaced through the hollow needle 6, which depends on the innerdiameter of the needle 6 and the viscosity of the drug. The needleinsertion depth is defined by the needle shield 4 abutting the indicatorring 2.2. The mating surfaces of the indicator ring 2.2 and the needleshield 4 visually and haptically indicate to the user that they areintended to be pushed completely together in order to correctly applythe drug delivery device 1.

Once insertion depth has been reached, further application of force ontothe outer body 3 in excess of the first detent force results indeformation of the resilient snap arms 2.6 so that the outer body 3decouples from the support body 2 and moves relative to the support body2 in the distal direction D thus also moving the stopper 7 within thesyringe barrel 5 so that the drug is displaced from the cavity throughthe injection needle 6. Near the end of the injection the stopper 7bottoms out in the syringe barrel 5. At the same time the outer body 3abuts the indicator ring 2.2 so that the drug delivery device 1 arrivesin a state as illustrated in FIG. 9. The mating surfaces of theindicator ring 2.2 and the outer body 3 visually and haptically indicateto the user that they are intended to be pushed completely together inorder to correctly apply the drug delivery device 1.

If the user removes the drug delivery device 1 from the injection sitethe needle shield 4 is no longer pushed against the skin and is henceextended in the distal direction D relative to the other components ofthe drug delivery device 1 by the needle shield spring 9 such that theinjection needle 6 arrives fully inside the needle shield 4 asillustrated in FIG. 10. During this movement the inward protrusion 4.7engages the proximal inclined section 2.3.3 and is deflected in a secondtangential direction T2 opposed to the first tangential direction T1.Once the inward protrusion 4.7 has travelled distally beyond theproximal inclined section 2.3.3 the retaining clips 4.5 are no longerdeflected. Hence, they will relax into the catch 2.3.4 thus locking theneedle shield 4 in position relative to the support body 2. The inwardprotrusion 4.7 and the retaining clips 4.5 are neither accessible forthe user nor can they be deflected out of the catch 2.3.4 in any otherway. Hence, the needle shield 4 is prevented from being depressed oncemore without destroying the drug delivery device 1.

The end of the outer body 3 coupled to the support body 2 may comprise aradially outwards directed flange 3.6 thus improving ergonomics whenapplying the drug delivery device 1.

In an exemplary embodiment a direction indicator 3.7 designed as aprofiled cavity or concavity in the surface of the outer body 3 isarranged in the range of the flange 3.6.

The needle shield 4 may likewise comprise a direction indicator 4.6.

A label retaining recess 3.8 may be arranged in the outer body 3 forreceiving a label which may be customized to the drug to be deliveredand/or to the provider of the drug.

FIG. 11 is a schematic view of the drug delivery device 1 with a bootremover 10 for removing the protective needle boot prior to aninjection. The boot remover 10 may be arranged to engage the needle bootby friction or by means of barbs. The boot remover 10 comprises a handleextending from the opening 4.3 for facilitating boot removal. Adirection indicator 10.1 may be provided on the boot remover 10 forindicating the direction in which the user has to move the boot remover10 for removing the protective needle boot.

1-15. (canceled)
 16. A drug delivery device comprising: a support bodyhaving a first end defining a first opening and a second end defining asecond opening, the support body configured to retain a syringe barrelsealed by a stopper slidably disposed therein along an axial directionand adapted to have an integrated needle or to be coupled with a needleassembly; and a needle shield configured to be coupled to the supportbody and slidably disposed thereon, the needle shield comprising adirection indicator.
 17. The device of claim 16, wherein the needleshield comprises a mating surface to couple to the support body.
 18. Thedevice of claim 16, further comprising a detent mechanism configured toconstrain movement of the needle shield relative to the support body byopposing the movement with a detent force.
 19. The device of claim 18,wherein the detent mechanism comprises at least one guiding trackdefined on the support body and at least one retaining clip on theneedle shield deflectable by the guiding track, wherein the guidingtrack is configured such that the retaining clip follows a first pathwhen the needle shield is depressed for needle extension and a differentsecond path when the needle shield is subsequently extended, wherein anon-return catch is arranged for catching the retaining clip at the endof the second path.
 20. The device of claim 16, wherein the support bodycomprises a guiding slot disposed within a wall of the support body, theguiding slot configured to guide movement of the needle shield.
 21. Adrug delivery device comprising: a support body having a first enddefining a first opening and a second end defining a second opening, thesupport body configured to retain a syringe barrel sealed by a stopperslidably disposed therein along an axial direction and adapted to havean integrated needle or to be coupled with a needle assembly; and aneedle shield configured to be coupled to the support body and slidablydisposed thereon, a boot remover configured to remove a protectiveneedle boot from a needle, the boot remover comprising a directionindicator.
 22. The device of claim 21, wherein the boot remover isconfigured to engage the needle boot by friction or by barbs.
 23. Thedevice of claim 21, wherein the boot remover comprises a handle tofacilitate boot removal.
 24. The device of claim 23, wherein the needleshield comprises an opening in which the needle boot is positioned,wherein the handle extends from the opening.
 25. A drug delivery devicecomprising: a support body having a first end defining a first openingand a second end defining a second opening, the support body configuredto retain a syringe barrel sealed by a stopper slidably disposed thereinalong an axial direction and adapted to have an integrated needle or tobe coupled with a needle assembly; and an outer body configured to becoupled to the support body and slidably disposed thereon, the outerbody comprising a direction indicator.
 26. The device of claim 25,wherein a portion of the outer body coupled to the support bodycomprises a radially outwards directed flange.
 27. The device of claim25, wherein the direction indicator comprises a profiled cavity orconcavity in a surface of the outer body.
 28. The device of claim 25,wherein the support body comprises a centered outer indicator ring,wherein the outer indicator ring limits a movement of the outer body.29. The device of claim 28, further comprising a detent mechanismconfigured to constrain movement of the outer body relative to thesupport body by opposing the movement with a detent force.
 30. Thedevice of claim 28, further comprising the syringe barrel sealed by thestopper and a plunger rod coupled to the stopper, a proximal portion ofthe plunger rod configured to be coupled to the outer body.